ROS-Responsive and active targeted drug delivery based on conjugated polymer nanoparticles for synergistic chemo-/photodynamic therapy.

Stimuli-responsive and active targeted drug release is highly significant and challenging for precise and effective cancer therapy. Herein, a reactive oxygen species (ROS)-responsive drug delivery system iRGD-BDOX@CPNs with active targeting for chemo-/photodynamic (PDT) synergistic therapy has been reported. This nanocarrier iRGD-BDOX@CPNs is constructed by the self-assembly of conjugated polymer poly(fluorene-co-vinylene) (PFV), prodrug BDOX (doxorubicin modified with a phenylboronic acid ester group) and an amphiphilic polymer (DSPE-PEG) modified with internalized RGD (DSPE-PEG-iRGD). The hydrophobic inner cores formed by PFV main chains tightly enclose BDOX. Due to PFV generating many ROS by light triggering, the BDOX prodrug can be in situ activated, resulting in the highly efficient drug release. In addition, the remarkable fluorescence recovery could be used for real-time monitoring of drug delivery and guiding antitumor therapy. Contributing to the specific recognition between iRGD and integrin αvß3 receptors over-expressed on the surface of tumor cells, the active targeting and uptake of iRGD-BDOX@CPNs in tumor cells are greatly enhanced. The prominent anti-cancer effect of iRGD-BDOX@CPNs is realized by targeted drug delivery and synergistic therapeutic effects of PDT/chemotherapy. This study illustrates that the development of ROS-responsive and targeted drug delivery nanocarriers iRGD-BDOX@CPNs provides a new insight for controllable drug release and tumor precision therapy.

Enhanced Energy Transfer in a Donor-Acceptor Photosensitizer Triggers Efficient Photodynamic Therapy.

Photosensitizers (PSs) play a vital role in photodynamic therapy (PDT) for combating bacterial resistance and treating tumor. In this study, we report new donor-acceptor porphyrin PSs with a cationic conjugated oligomer (OPV) as a donor unit and porphyrin (TPP) as an acceptor unit by covalent linkage and achieved a fluorescence resonance energy transfer efficiency of 99% owing to their strong spectral overlap and short distance. The 1O2 yield of porphyrin derivatives is 121% (rose bengal as the standard reference) by virtue of OPVs' excellent light-harvesting ability and high fluorescence resonance energy transfer efficiency, greatly exceeding those of oligomer and porphyrin derivatives reported in the literature. Additionally, the cationic donors significantly improved the water solubility, decreased the aggregation of porphyrin, and promoted the adherence of the PSs to cell membranes through electrostatic interactions. As a result, the D-A porphyrin PSs exhibit dramatic PDT treatment efficiency. The half-inhibitory concentration is as low as 33 and 88 nM for methicillin-resistant Staphylococcus aureus and Escherichia coli, respectively. Therefore, this study provides a new strategy to construct PSs with high 1O2 yield and an excellent treatment effect at a low dose of PSs, which is promising for application in PDT used to treat cancer and microbial infections.

Amino Acid-Modified Conjugated Oligomer Self-Assembly Hydrogel for Efficient Capture and Specific Killing of Antibiotic-Resistant Bacteria.

Bacterial infection is one of main causes that threaten global human health. Especially, antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) lead to high mortality rate and more expensive treatment cost. Here, a novel amino-acid-modified conjugated oligomer OTE-d-Phe was synthesized by modifying the side chain of conjugated oligo(thiophene ethynylene) with d-phenylalanine. By mixing 9-fluorenylmethyloxycarbonyl-l-phenylalanin (Fmoc-l-Phe) with OTE-d-Phe, a new and biocompatible low-molecular weight hydrogel (HG-2) was prepared through self-assembly. In solution, HG-2 can effectively capture bacteria spontaneously, such as Escherichia coli and MRSA. Most importantly, the hydrogel has specific and strong antibacterial activity against MRSA over methicillin-susceptible S. aureus, Staphylococcus epidermidis, and E. coli. Interestingly, when the hydrogel was put on a model surface, a piece of cloth, it also is able to selectively kill MRSA with low cell cytotoxicity. The antibacterial mechanism was investigated, and it demonstrated that the HG-2 interacts with and physically breaks the cell wall and membrane, which leads to MRSA death. Therefore, this new conjugated oligomer-based hydrogel provides promising applications in disinfection and therapy of MRSA in hospital and in community.

Conjugated Polymers-Based Thermal-Responsive Nanoparticles for Controlled Drug Delivery, Tracking, and Synergistic Photodynamic Therapy/Chemotherapy.

Stimuli-responsive multifunctional nanomaterials have attracted much attention due to drug release on-demand for cancer therapy. In this study, the thermal-responsive nanoparticles are prepared based on cationic conjugated poly(fluorene-co-vinylene) (PFV), temperature-responsive poly(N-isopropylacrylamide) (PNIPAM), and antitumor model drug doxorubicin (DOX). Interestingly, the nanoparticles possess multiple functions including thermoresponsive drug release, cell imaging, and chemo- and photodynamic synergistic therapy. The drug is released efficiently above the lower critical solution temperature (LCST) of PNIPAM, and more than 70% of the loaded drugs were delivered at pH 5.5 and 37 °C. Importantly, the drug release process can be tracked by fluorescent imaging owing to the bright fluorescence of conjugated polymer-based nanoparticles. Specifically, conjugated polymer PFV acts as a photosensitizer to produce high reactive oxygen species under white light irradiation, bringing an effective chemo-/photodynamic therapy (PDT) synergistic effect. The cell viability of MCF-7 decreases to only 3.2% after treating with PNIPAM-DOX-CPNs (conjugated polymer nanoparticles) under white irradiation, which is much lower than that with a single treatment. Therefore, the multifunctional nanoparticles provide a promising platform for controllable drug delivery, tracking, and tumor therapy in biomedical applications.

Fluorescent Conjugated Polymer/Quarternary Ammonium Salt Co-assembly Nanoparticles: Applications in Highly Effective Antibacteria and Bioimaging.

Bacterial resistance is one of the very severe factors that threaten human health. It is of great significance to construct a simple, highly effective, biocompatible, and cost-efficient therapeutic route. In this paper, a new method was constructed to prepare cationic nanoparticles, and fluorescent conjugated polymer coassembly nanoparticles CA-CPNs were designed and synthesized on the basis of the model conjugated polymers, PFVBT, and the model quarternary ammonium salts, cationic surfactant cetyltrimethylammonium bromide CTAB. PFVBTs were designed and synthesized in only three steps. CTAB is commercially available. By the reprecipitation method, the PFVBTs form the core and CTAB forms a shell on the surface of CA-CPNs by hydrophobic interaction. Importantly, when incubated with bacteria, the positively charged CA-CPNs can combine with bacteria, physically destroy the bacterial membrane, and kill bacteria without the requirement of light or chemical energy. When 0.80 µg/mL CA-CPNs were incubated for 30 min with Escherichia coli, more than 91% bacteria were killed. Also, more than 96% Staphylococcus aureus were dead when incubated with 1.0 µg/mL CA-CPNs. In virtue of the bright red fluorescence, CA-CPNs were also successfully applied to image MCF-7 cell with good biocompatibility. Overall, a simple, cost-effective, and universal method was provided to prepare cationic fluorescent nanoparticles that are a promising nanomaterial for biomedical applications.